PAC, consists the ADCs linker and PROTACs, conjugated to an antibody. PAC extracts from patent WO2017201449A1, compound LP2. PAC conjugated to an antibody is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).
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Cas No.: 2158322-33-7
Sample solution is provided at 25 µL, 10mM.
GlpBio Products Cited In Reputable Papers
Syntheses of a PAC:A. Chemical Synthesis of a PROTAC:i. Attachment of a Linker (L2) to an E3 Ligase Binding Group (E3LB).ii. Attachment of a protein binding moiety (PB) to an E3LB via a Linker (L2).B. Preparation of L1-PROTAC:iii. Attachment of Linker L1 to PROTAC.C. Preparation of PAC: iv. Attachment of Antibody (Ab) to PROTAC via Linker L1.
. Thomas Pillow, et al. Protac antibody conjugates and methods of use. WO2017201449A1.
PAC comprises an antibody conjugated via a linker to a PROTAC. PAC extracts from patent WO2017201449A1, compound PAC1. PAC is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).
Treatment of HER2 expressing cells with HER2 antibody containing PAC Anti-HER2(Endox-XIAP) results in a marked decreased Estrogen Receptor-alpha (ERα) levels with an IC50 of 132 ng/mL. The PROTAC-Antibody Conjugate (PAC) molecules comprise an antibody conjugated via a linker (L1) to a PROTAC, wherein the PROTAC comprises an ubiquitin E3 ligase binding group ("E3LB"), a linker ("L2") and a protein binding group ("PB"). The following sections describe the components that comprise the PAC. To obtain a PAC having potent efficacy and a desirable therapeutic index, the following components are provided. 1. Antibody (Ab): The antibody portion of a PAC can target a cell that expresses an antigen whereby the antigen specific PAC is delivered intracellularly to the target cell, typically through endocytosis While PACs that comprise an antibody directed to an antigen that is not found on the cell surface may result in less specific intracellular delivery of the PROTAC portion into the cell, the PAC may still undergo pinocytosis. 2. Linkers (L1): A"linker" (L1) is a bifunctional or multifunctional moiety that can be used to link one or more PROTAC moieties (D) to an antibody (Ab) to form a PAC. In some embodiments, PACs can be prepared using a L1 having reactive functionalities for covalently attaching to the PROTAC and to the antibody. 3. PROTAC(D) .
. Thomas Pillow, et al. Protac antibody conjugates and methods of use. WO2017201449A1.
|DMSO: 100 mg/mL (59.70 mM); Water: < 0.1 mg/mL (insoluble)
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|Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
|Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.
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Non-pharmacological remedies for post-viral acute cough
Monaldi Arch Chest Dis 2021 Aug 10;92(1).PMID:34461702DOI:10.4081/monaldi.2021.1821.
The post-viral acute cough (PAC) is a widespread symptom, mainly in childhood and adolescence, and is usually associated with an acute upper respiratory infection, namely the common cold. The use of cough relievers is, therefore, impressive, as documented by the market data. There are many medical devices and dietary supplements for treating PAC, which contain non-pharmacological components. Ancient people used traditional herbs to treat PAC. Thus, a well-established tradition considers natural remedies as an effective and safe way to relieve PAC. The herbal agents include polyphenols, flavonoids, saponins, glucosides, and alkaloids. Also, the European Medicine Agency has recognized the value of plant extracts and other natural substances to treat PAC. Nevertheless, a few studies investigated the role of non-pharmacologic remedies for PAC. There is some evidence for honey, glycerol, Althea officinalis, Drosera rotundifolia, Grindelia, Hedera helix, Pelargonium sidoides, Sambucus nigra, Thymus vulgaris, hyaluronic acid, and saline solutions. However, further rigorous studies should confirm natural products' efficacy and safety to relieve PAC.
Invasive hemodynamic monitoring
Crit Care Clin 2015 Jan;31(1):67-87.PMID:25435479DOI:10.1016/j.ccc.2014.08.004.
Although invasive hemodynamic monitoring requires considerable skill, studies have shown a striking lack of knowledge of the measurements obtained with the pulmonary artery catheter (PAC). This article reviews monitoring using a PAC. Issues addressed include basic physiology that determines cardiac output and blood pressure; methodology in the measurement of data obtained from a PAC; use of the PAC in making a diagnosis and for patient management, with emphasis on a responsive approach to management; and uses of the PAC that are not indications by themselves for placing the catheter, but can provide useful information when a PAC is in place.
CRC-Aided Adaptive BP Decoding of PAC Codes
Entropy (Basel) 2022 Aug 22;24(8):1170.PMID:36010834DOI:10.3390/e24081170.
Although long polar codes with successive cancellation decoding can asymptotically achieve channel capacity, the performance of short blocklength polar codes is far from optimal. Recently, Arıkan proposed employing a convolutional pre-transformation before the polarization network, called polarization-adjusted convolutional (PAC) codes. In this paper, we focus on improving the performance of short PAC codes concatenated with a cyclic redundancy check (CRC) outer code, CRC-PAC codes, since error detection capability is essential in practical applications, such as the polar coding scheme for the control channel. We propose an enhanced adaptive belief propagation (ABP) decoding algorithm with the assistance of CRC bits for PAC codes. We also derive joint parity-check matrices of CRC-PAC codes suitable for iterative BP decoding. The proposed CRC-aided ABP (CA-ABP) decoding can effectively improve error performance when partial CRC bits are used in the decoding. Meanwhile, the error detection ability can still be guaranteed by the remaining CRC bits and adaptive decoding parameters. Moreover, compared with the conventional CRC-aided list (CA-List) decoding, our proposed scheme can significantly reduce computational complexity, to achieve a better trade-off between the performance and complexity for short PAC codes.
Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial
Lancet 2005 Aug;366(9484):472-7.PMID:16084255DOI:10.1016/S0140-6736(05)67061-4.
Background: Over the past 30 years the pulmonary artery catheter (PAC) has become a widely used haemodynamic monitoring device in the management of critically ill patients, though doubts exist about its safety. Our aim was, therefore, to ascertain whether hospital mortality is reduced in critically ill patients when they are managed with a PAC. Methods: We did a randomised controlled trial to which we enrolled 1041 patients from 65 UK intensive care units. We assigned individuals to management with (n=519) or without (n=522) a PAC. The timing of insertion and subsequent clinical management were at the discretion of the treating clinician. Intensive care units decided a priori to have the option of using an alternative cardiac output-monitoring device in control patients. Findings: 1014 patients were eligible for analysis. We noted no difference in hospital mortality between patients managed with or without a PAC (68% [346 of 506] vs 66% [333 of 507], p=0.39; adjusted hazard ratio 1.09, 95% CI 0.94-1.27). We noted complications associated with insertion of a PAC in 46 of 486 individuals in whom the device was placed, none of which was fatal. Interpretation: Our findings indicate no clear evidence of benefit or harm by managing critically ill patients with a PAC. Efficacy studies are needed to ascertain whether management protocols involving PAC use can result in improved outcomes in specific groups if these devices are not to become a redundant technology.
List Decoding of Arıkan's PAC Codes
Entropy (Basel) 2021 Jun 30;23(7):841.PMID:34209050DOI:10.3390/e23070841.
Polar coding gives rise to the first explicit family of codes that provably achieve capacity with efficient encoding and decoding for a wide range of channels. However, its performance at short blocklengths under standard successive cancellation decoding is far from optimal. A well-known way to improve the performance of polar codes at short blocklengths is CRC precoding followed by successive-cancellation list decoding. This approach, along with various refinements thereof, has largely remained the state of the art in polar coding since it was introduced in 2011. Recently, Arıkan presented a new polar coding scheme, which he called polarization-adjusted convolutional (PAC) codes. At short blocklengths, such codes offer a dramatic improvement in performance as compared to CRC-aided list decoding of conventional polar codes. PAC codes are based primarily upon the following main ideas: replacing CRC codes with convolutional precoding (under appropriate rate profiling) and replacing list decoding by sequential decoding. One of our primary goals in this paper is to answer the following question: is sequential decoding essential for the superior performance of PAC codes? We show that similar performance can be achieved using list decoding when the list size L is moderately large (say, L⩾128). List decoding has distinct advantages over sequential decoding in certain scenarios, such as low-SNR regimes or situations where the worst-case complexity/latency is the primary constraint. Another objective is to provide some insights into the remarkable performance of PAC codes. We first observe that both sequential decoding and list decoding of PAC codes closely match ML decoding thereof. We then estimate the number of low weight codewords in PAC codes, and use these estimates to approximate the union bound on their performance. These results indicate that PAC codes are superior to both polar codes and Reed-Muller codes. We also consider random time-varying convolutional precoding for PAC codes, and observe that this scheme achieves the same superior performance with constraint length as low as ν=2.
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